PROJECT SUMMARY/ABSTRACT A significant number of children with ASD remain minimally verbal even after receiving quality interventions. Recent studies have highlighted the heterogeneity of this group confirming that no single mechanism can explain the underlying causes of their severe communication deficits. At the same time, innovative targeted behavioral interventions can lead to improvements in speech and social communication in some minimally verbal children. The goals of this Center, located at Boston University and University of California Los Angeles, are to build on our earlier work addressing a central theme: Which young minimally verbal children with ASD make gains acquiring language during the early school years and how can we facilitate such progress? We approach these questions from a multidisciplinary perspective, employing tools, methods, and approaches drawn from communication disorders, speech and motor science, developmental neuroscience, genetics and interventions research. The four interconnected projects address the following aims. Aim 1: To identify motor and neural mechanisms underlying the profound spoken language impairments that define minimally verbal children with autism. In two projects on the same group of young minimally verbal children we plan to characterize oral and general motor functioning using state-of- the-art technologies, and electrophysiology to probe neural functioning (Project 1, 2). Aim 2: To advance our understanding of how to optimize the language outcomes of young minimally verbal children with ASD. We address this by carrying out a randomized controlled trial of a behavioral intervention that combines social communication and oromotor targets (Project 3) and by following the children studied in Aim 1 for two years to explore how changes in motor and neural functioning may predict diverse language pathways (Projects 1, 2). Aim 3: To investigate genetic risk factors associated with minimally verbal ASD, including both common and rare variants (Project 4). We plan to leverage the children enrolled in all the projects to explore the relationship between the quantitative load for common polygenic risk for ASD and language, motor, and neural phenotypes as well as genetic predictors of response to treatment and more optimal developmental outcomes (all Projects). The projects are united and served by an Administrative Core (A) and a Clinical and Data Management Scientific Core (B) that will carry out comprehensive assessments using available and novel measures to capture the heterogeneous phenotypes of minimally verbal children with ASD. Together, the research conducted in our Center will significantly advance our understanding of the profound communication deficits at this neglected end of the autism spectrum, develop behavioral and neural biomarkers that predict different developmental pathways for language, and may highlight potential molecular targets for future novel therapeutic interventions.